The Endotoxin Hypothesis of Parkinson's Disease

[Bolt_Upright]

Abstract: The endotoxin hypothesis of Parkinson's disease (PD) is the idea that lipopolysaccharide (LPS) endotoxins contribute to the pathogenesis of this disorder. LPS endotoxins are found in, and released from, the outer membrane of Gram-negative bacteria, for example in the gut. It is proposed that gut dysfunction in early PD leads to elevated LPS levels in the gut wall and blood, which promotes both α-synuclein aggregation in the enteric neurons and a peripheral inflammatory response. Communication to the brain via circulating LPS and cytokines in the blood and/or the gut–brain axis leads to neuroinflammation and spreading of α-synuclein pathology, exacerbating neurodegeneration in brainstem nuclei and loss of dopaminergic neurons in the substantia nigra, and manifesting in the clinical symptoms of PD. The evidence supporting this hypothesis includes: (1) gut dysfunction, permeability, and bacterial changes occur early in PD, (2) serum levels of LPS are increased in a proportion of PD patients, (3) LPS induces α-synuclein expression, aggregation, and neurotoxicity, (4) LPS causes activation of peripheral monocytes leading to inflammatory cytokine production, and (5) blood LPS causes brain inflammation and specific loss of midbrain dopaminergic neurons, mediated by microglia. If the hypothesis is correct, then treatment options might include: (1) changing the gut microbiome, (2) reducing gut permeability, (3) reducing circulating LPS levels, or (4) blocking the response of immune cells and microglia to LPS. However, the hypothesis has a number of limitations and requires further testing, in particular whether reducing LPS levels can reduce PD incidence, progression, or severity. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Full Article: movementdisorders.onlinelib...

[park_bear]

The biological system for handling alpha synuclein is a kluge that barely works even under good circumstances. As a result there are over 20 different mutations that can cause Parkinson's as well as the number of toxic substances. LPS is a highly inflammatory substance. It could well also be a cause of Parkinson's.

[MarionP in reply to park_bear]

Certainly sounds feasible.

[LAJ12345]

selfhacked.com/blog/reduce-....

“Takeaway

Lipopolysaccharides (LPS) are bacterial toxins that may enter the blood if you have an infection or “leaky gut.”

Limited research has associated LPS with many chronic health problems–from heart disease to diabetes to IBS to sleep issues.

These small particles are thought to trigger systemic inflammation and other nonspecific symptoms. For example, scientists can use LPS to experimentally induce fatigue, poor memory, anxiety, and social disconnection.

However, more research is needed to understand if LPS plays a significant role in causing any disease.

Potential healthy ways to reduce LPS include cooking with olive oil and eating foods high in pre- and probiotics, polyphenols, and omega-3 fatty acids. Meditation and vagus nerve stimulation might also help, according to limited research data.”

[goldengrove]

Thanks for posting this very interesting article.

[Likii]

Allithiamine Exerts Therapeutic Effects on Sepsis by Modulating Metabolic Flux during Dendritic Cell Activation

Eun Jung Choi 1 2 3, Chang Hyun Jeon 1 3, Dong Ho Park 4, Tae-Hwan Kwon 1 2

Free PMC article

... First, using allithiamine, which showed the most potent anti-inflammatory capacity among thiamine derivatives, we confirmed the inhibitory effects of allithiamine on the lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and maturation process in dendritic cells. We applied the LPS-induced sepsis model to examine whether allithiamine has a protective role in hyper-inflammatory status ...

pubmed.ncbi.nlm.nih.gov/332...

[Gioc in reply to Likii]

Molto interessante, Likii

anche se io continuo a pensare che la b3 NA possa fare meglio e ultimamente sto ottenendo buoni risultati con l’oleuropeine ( Idrossitirosolo ) estratto di foglie di olive. L’oleuropeina é poco studiato ma molto interessante per il PD , (alfasyn riduzione (?), inibitore della MaO e potente antinfiammatorio , qualche effetto collaterale ( abbassa la pressione sanguigna) ☹️,poi basta).

[Bolt_Upright in reply to Gioc]

Good stuff Gioc. I hope you don't mind my Google Translating it:

"Very interesting, Likii

although I still think that b3 NA can do better and lately I have been getting good results with oleuropeine (Hydroxytyrosol) olive leaf extract. Oleuropein is little studied but very interesting for PD, (alfasyn reduction (?), MaO inhibitor and powerful anti-inflammatory, some side effects (lowers blood pressure) ☹️, then that's it)."

Bolt says: I still use B3 NA

[Gioc in reply to Bolt_Upright]

Thanks, you translated much better than I can.

A curiosity that I can't evaluate the importance of:

Hydroxytyrosol (oleuropeina) It is a molecule almost the same as dopamine but it seems to pass the BBB.

This would seem irrelevant, just a simple curiosity of no practical use confirmed.

C8 H10 O3 Hydroxytyrosol

C₈ H₁₁ NO₂ Dopamine

* correction: in reality they are chemically very different molecules: hydroxytyrosol is a phenolic compound, while dopamine is a neurotransmitter belonging to the catecholamine class.